Heterotrophic microbes initiate the degradation of high molecular weight organic matter using extracellular enzymes. Our understanding of differences in microbial enzymatic capabilities, especially among particle-associated taxa and in the deep ocean, is limited by a paucity of hydrolytic enzyme activity measurements. Here, we measured the activities of a broad range of hydrolytic enzymes (glucosidases, peptidases, polysaccharide hydrolases) in epipelagic to bathypelagic bulk water (nonsize-fractionated), and on particles (≥ 3 μm) along a 9800 km latitudinal transect from 30°S in the South Pacific to 59°N in the Bering Sea. Individual enzyme activities showed heterogeneous latitudinal and depth-related patterns, with varying biotic and abiotic correlates. With increasing latitude and decreasing temperature, lower laminarinase activities sharply contrasted with higher leucine aminopeptidase (leu-AMP) and chondroitin sulfate hydrolase activities in bulk water. Endopeptidases (chymotrypsins, trypsins) exhibited patchy spatial patterns, and their activities can exceed rates of the widely measured exopeptidase, leu-AMP. Compared to bulk water, particle-associated enzymatic profiles featured a greater relative importance of endopeptidases, as well as a broader spectrum of polysaccharide hydrolases in some locations, and latitudinal and depth-related trends that are likely consequences of varying particle fluxes. As water depth increased, enzymatic spectra on particles and in bulk water became narrower, and diverged more from one another. These distinct latitudinal and depth-related gradients of enzymatic activities underscore the biogeochemical consequences of emerging global patterns of microbial community structure and function, from surface to deep waters, and among particle-associated taxa.